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Updated: Jun 9, 2025
Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
Characterizing and Targeting of BCL-2 Family Members in Nasopharyngeal Carcinoma
A A Thai1,2,3, R J Young3, M Bressel2,4
1Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
Background:
The success of BH3 mimetics in hematological malignancies has spurred interest in their application in solid tumors. We examined the expression of the BCL-2 family of molecules in NPC tumors and cell lines and explored the anticancer efficacy of BH3 mimetics in vitro.
Methods:
Immunohistochemistry for BCL-2, MCL-1, BCL-xL, and transcriptomic analyses was conducted on NPC tumors. The efficacy of ABT-199, S63845, and ABT-737 were examined as monotherapy and in combination with cisplatin in NPC cell lines. RNA sequencing was performed to identify up and downregulated pathways in sensitive cell lines.
Results:
One hundred and forty-nine EBV-positive NPC and 15 EBV-negative NPC were identified. Expression of BCL-2 was more frequent in EBV-positive NPC. BCL-2, MCL-1, and BCL-xL expression was not prognostic for overall survival. Marked sensitivity was seen with the combination of S63845 and cisplatin in NPC43.
Conclusion:
Our study demonstrates the therapeutic potential of combining cisplatin and S63845, which warrants further investigation.
Insights
Combining BH3 mimetics like S63845 with cisplatin shows promise for treating nasopharyngeal carcinoma (NPC). This combination therapy warrants further clinical investigation for solid tumors.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- BH3 mimetics are successful in hematological cancers, driving interest in their use for solid tumors.
- Nasopharyngeal carcinoma (NPC) is a solid tumor where BCL-2 family molecule expression and BH3 mimetic efficacy require investigation.
Purpose of the Study:
- To examine BCL-2 family molecule expression in NPC.
- To explore the in vitro anticancer efficacy of BH3 mimetics in NPC cell lines, alone and with cisplatin.
Main Methods:
- Immunohistochemistry and transcriptomic analysis of NPC tumors for BCL-2, MCL-1, and BCL-xL.
- In vitro testing of BH3 mimetics (ABT-199, S63845, ABT-737) as monotherapy and in combination with cisplatin in NPC cell lines.
- RNA sequencing to identify pathways in sensitive cell lines.
Main Results:
- BCL-2 expression was more common in EBV-positive NPC.
- BCL-2, MCL-1, and BCL-xL expression levels did not predict overall survival.
- The combination of S63845 and cisplatin demonstrated significant sensitivity in the NPC43 cell line.
Conclusions:
- The combination of cisplatin and S63845 exhibits therapeutic potential in NPC.
- Further investigation into this combination therapy for NPC is warranted.
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